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| Status |
Public on Sep 01, 2011 |
| Title |
Pten deficiency cooperates with KrasG12D to activate NFkB pathway promoting the development of malignant pancreatic ductal adenocarcinoma |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Almost all human pancreatic ductal adenocarcinomas (PDACs) are driven by oncogenic Kras and the progression of the disease is characterized by the serial appearance of certain genetic lesions. Mouse models have convincingly shown that Kras mutation induces classical PanIN lesions that can progress to PDAC in the appropriate tumor suppressor background. However, the cooperative mechanism between mutant Kras-dependent signaling surrogates and other oncogenic pathways remains to be fully elucidated in order to devise better therapeutic strategy. Mounting evidence PTEN/PI3K perturbation on PDAC tumorigenesis, we observed frequent PTEN inactivation at both genomic and histopathological levels in primary human PDAC samples. The importance of PTEN/PI3K pathway during the development of PDAC was further supported by genetic studies demonstrating that Pten deficiency in cooperation with Kras activation accelerated the formation of invasive PDAC. Mechanistically, combined Kras mutation and Pten inactivation leads to NFkB activation and subsequent induction of cytokine pathways, accompanied with strong stromal activation and immune cell infiltration. Therefore, PTEN/PI3K pathway dictates the activity of NFkB network and serves as a major surrogate during Kras-mediated pancreatic tumorigenesis.
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| Overall design |
Primary pancreatic ductal epithelial cell cultures were established from 6 week old Pdx1-Cre;LSL-KrasG12D L/+ (n=3) or Pdx1-Cre;LSL-KrasG12D L/+;Pten L/+ (n=5) mice. Total RNA was collected from early passage cells.
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| |
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| Citation(s) |
21984975 |
| Submission date |
Dec 02, 2010 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Haoqiang Ying |
| E-mail(s) |
haoqiang_ying@dfci.harvard.edu
|
| Phone |
617-582-7978
|
| Fax |
617-632-6069
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Medical Oncology
|
| Lab |
Ronald DePinho
|
| Street address |
44 Binney St.
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA135737 |
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